Bone Resorption and Environmental Exposure to Cadmium in Women: A Population Study

Abstract

BackgroundEnvironmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction.ObjectiveWe sought evidence for a direct osteotoxic effect of cadmium in women.MethodsWe randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density.ResultsIn all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, –0.009 g/cm2 (p = 0.055) for proximal forearm bone density, and –16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were –0.01223 g/cm2 (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, –9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 μg/day).ConclusionsIn the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.

Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women

“…unlikely to be the proposed link between Cd-induced effects on kidney and bone. (33) Furthermore, the positive association between U-Cd and urinary calcium observed previously (26,29,30) and in this study has been considered a result of Cd-induced tubular damage causing hypercalciuria but may well be a result of Cd-induced increased bone resorption. (29,30) U-Cd also has been shown to be associated with both increased bone resorption and decreased parathyroid hormone concentrations, (6,26) suggesting that the effect on bone was not mediated primarily by Cd-induced tubular damage.…”

“…Human data support Cdinduced increased bone resorption rather than an effect on bone formation. (6,29,30) Our results on fracture risk suggest, however, that Cd's effect is only partly mediated via lowered BMD. It can be speculated that Cd exposure also results in specific effects on cortical and trabecular bone or in alterations of biomechanical properties that are not detected by DXA; this is also supported by experimental studies.…”

Occupational cadmium exposure and calcium excretion, bone density, and osteoporosis in men

“…(7) Studies among populations from Belgium, (4,8) Sweden, (9)(10)(11) Japan, (12) and China (13,14) showed associations between osteoporosis and low-level environmental cadmium exposure. The generally accepted interpretation has been that cadmiuminduced renal tubular damage (2) decreases the calcium reabsorption in the nephron, resulting in hypercalciuria (2) and low BMD and hence increased fracture risk, (4,11) particularly in postmenopausal women (4,8) or men in the older age group. (11) In keeping with experimental studies, this study supports indirectly the interpretation that cadmium decreases bone density and increases the risk of osteoporosis through a direct osteotoxic effect.…”

Cadmium exposure in the population: from health risks to strategies of prevention

“…Studies among populations from Belgium (Staessen et al 1999;Schutte et al 2008b), Sweden (Järup et al 1998a;Alfvén et al 2000;Å kesson et al 2006), Japan and China Jin et al 2004;Wang et al 2003) showed associations between osteoporosis and low-level environmental Cd exposure. The generally accepted interpretation has been that Cd-induced renal tubular damage (Staessen et al 1994) decreases the calcium reabsorption in the nephron, resulting in hypercalciuria and decreased bone mineral density, and hence increased fracture risk (Järup et al 1998c;Staessen et al 1994) particularly in postmenopausal women (Schutte et al 2008b;Staessen et al 1999) or men in the older age group . However, a recent study also found a dose-response association between odds of osteoporosis in young men (mean age 45) and urinary Cd .…”

“…Dose-response relationships were reported on urinary Cd as a continuous variable expressed in lg per g creatinine [OR = 1.15 (95% CI 1.00-1.33)]. Recent data provide more insight into the mechanisms supporting a direct osteotoxic effect of Cd independent of the status of kidney function in that urinary excretion of pyridinium crosslinks from bone collagen is increased (Schutte et al 2008b). The shape of this association was linear with effects observed at low levels ( Table 1).…”